ライフサイエンスコーパス: TACI

1 TACI binds the cytokines BAFF and APRIL, and previous st

2 TACI binds two ligands, APRIL and BAFF, with high affini

3 TACI is a member of the tumor necrosis factor receptor s

4 TACI is likely to influence Mvarphi phenotype by mediati

5 TACI lacks a TIR domain, yet triggered CSR via the DNA-e

6 TACI proteolysis involved shedding by a disintegrin and

7 TACI's role is controversial based on defects in TI anti

8 TACI(+) transitional cells from BAFF-transgenic mice are

9 TACI(-/-) mice develop fatal autoimmune glomerulonephrit

10 TACI-driven proliferation, isotype switching, and antibo

11 TACI-Fc (atacicept), a soluble fusion protein containing

12 TACI-Ig treatment normalized serum levels of IgM that ar

13 TACI-induced CSR was impaired in mice and humans lacking

14 osis factor receptor superfamily member 13B (TACI) ligation.

15 Importantly, a TACI (trans-membrane activator and CAML interactor)-Fc f

16 s p70S6 kinase and 4E-binding protein 1 in a TACI-dependent manner.

17 atient follicular lymphoma (FL) B cells in a TACI-dependent manner.

18 Atacicept is a TACI-Ig fusion protein that inhibits B cell stimulation

19 Moreover, low doses of a TACI fusion protein (TACI-Fc) that express the extracell

20 normal individuals harbor the C140R or A181E TACI variants and have no outward signs of CVID, and it

21 ygosity for A144E in mice resulted in absent TACI expression in B cells, indicating that the mutant p

22 Additionally, TACI expression seems to be important in plasma cell dev

23 t loss of a TNFRSF13B allele does not affect TACI expression, activation responses, or establishment

24 We found that B1b cells express BAFFR and TACI and that the surface expression of both receptors i

25 To examine the role of BAFFR and TACI in T cell-independent antibody responses to an acti

26 known as BLyS, with its receptors BAFFR and TACI on B cells is critical for B cell homeostasis and f

27 BCMA and TACI additionally bind APRIL (a proliferation-inducing l

28 edundant: BAFFR binds BAFF, whereas BCMA and TACI bind to either BAFF or APRIL.

29 ave used these ligands to show that BCMA and TACI have a distinct role in APRIL-induced B cell stimul

30 is of primary tumor expressing both BCMA and TACI in the presence of a BCMA-targeting antibody.

31 ntified surface tumor expression of BCMA and TACI on primary MM cells (n = 50).

32 ifferent affinity to two receptors, BCMA and TACI, and induce cell survival and/or proliferation, whe

33 ceptors B-cell maturation antigen (BCMA) and TACI with high affinity; both of these receptors have al

34 ntibodies to the receptors BAFF-R, BCMA, and TACI were used to define expression of the individual BL

35 eract with three receptors, BAFFR, BCMA, and TACI, to play discrete and crucial roles in regulating B

36 rance, binds three receptors: BR3, BCMA, and TACI.

37 L binds to the receptors BCMA on B cells and TACI on B and T cells.

38 cannot generate CTLs in B-cell-deficient and TACI-deficient mice, strongly supporting a need for B-ce

39 protein antigens in both TACI-deficient and TACI-proficient mice.

40 These variants impair TACI function, and TACI-deficient mice exhibit a CVID-like disease.

41 whereas several mutations (CYLD, NFKB1, and TACI) selectively activate the classical pathway.

42 wed enriched expression of CHIT1, TGFB1, and TACI in NMZL, and BCL6, LMO2, and CD10 in FL.

43 ACI expression and whether an agonistic anti-TACI antibody could induce activation-induced cytidine d

44 er, its effectiveness is neutralized by anti-TACI antibodies when present.

45 )F(1) mice, AdTACI induced neutralizing anti-TACI antibodies and failed to reduce the numbers of B ce

46 eceptors that recognize both BAFF and APRIL, TACI (transmembrane-activator-1 and calcium-modulator- a

47 mall-interfering RNAs targeting BAFF, APRIL, TACI, and BCMA inhibited HRS cell accumulation in vitro

48 studies are the first to characterize APRIL-TACI-specific signaling and suggest a role for this liga

49 sought to characterize the outcome of APRIL-TACI interactions.

50 an important role in CLL and that the APRIL-TACI interaction might be a selective novel therapeutic

51 A144E heterozygous mice, such as TACI(+/-) mice, expressed half the normal level of TACI

52 has important implications for asymptomatic TACI A181E carriers.

53 only TLR4 relies on c-Rel and p50 to augment TACI expression, whereas TLR9 does not.

54 ution to BAFF-mediated humoral autoimmunity, TACI(+) transitional B cells from BAFF-transgenic mice s

55 mice demonstrates that BAFF-BCMA and/or BAFF-TACI interactions contribute to SLE, and that a profound

56 eporter cell line assays specific for BAFFR, TACI, or BCMA.

57 lete ACAR-mediated tumor clearance of BCMA(+)TACI(-) and BCMA(-)TACI(+) cells, and a single-chain var

58 tumor clearance of BCMA(+)TACI(-) and BCMA(-)TACI(+) cells, and a single-chain variable fragment CAR

59 BCMA, TACI, and B lymphocyte stimulator receptor 3 (BR3) were

60 ssed one or more of 3 known receptors (BCMA, TACI, and BAFF-R) for BLyS; however, the pattern of expr

61 gand TALL-1 and its cognate receptors, BCMA, TACI and BAFF-R, were recently identified as members of

62 in CLL cells, whereas signaling through BCMA/TACI induced activation of the canonical NF-kappaB pathw

63 cts at a remote time from activation because TACI is not necessary for activation and proliferation o

64 gly, some individuals with mutations in both TACI alleles do not present with CVID, suggesting that T

65 tion of immunity to protein antigens in both TACI-deficient and TACI-proficient mice.

66 Also, mice lacking both TACI and BCMA simultaneously exhibit no B cell loss, thu

67 The results obtained indicate that both TACI and BAFF-R are able to transduce signals that resul

68 he mechanism that underlies CSR signaling by TACI remains unknown.

69 Interruption of BAFF and APRIL signaling by TACI-Ig decoy receptor, which binds to and neutralizes B

70 stic insight into how the heterozygous C104R TACI mutation can potentially lead to CVID.

71 or 9 triggering normally up-regulates B-cell TACI expression, this was defective for all subjects wit

72 Finally, a short course of combination TACI-Ig and CTLA4-Ig prolonged life and even reversed pr

73 One of the 2 most common TACI mutations in CVID, A181E, introduces a negative cha

74 In contrast, TACI-deficient mice immunized with heat-killed type 3 se

75 ouse to TI-2 Ags and BCR activation controls TACI expression.

76 ly healthy subjects and of the corresponding TACI A144E mutation in mice.

77 f a TNFRSF13B allele did result in decreased TACI expression on memory B cells, resulting in impaired

78 FF promotes humoral autoimmunity via direct, TACI-dependent activation of transitional B cells.

79 on and its human counterpart, A181E, disrupt TACI signaling and impair TACI-dependent B-cell function

80 TNFRSF13B, which encodes TACI (transmembrane activator and calcium-modulator and

81 utation in one allele of TNFRSF13B (encoding TACI).

82 ls by producing BAFF and APRIL, which engage TACI, BCMA, and BAFF-R receptors on the B cells.

83 erentiation earlier during clonal expansion, TACI may decrease the chances of autoantibody production

84 ed BCMA, and 39 (78%) of them also expressed TACI.

85 sors, HRS cells lacked BAFF-R, but expressed TACI and BCMA, a phenotype similar to that of plasmacyto

86 om individuals with TACI mutations expressed TACI but did not produce IgG and IgA in response to the

87 Intracellular and extracellular TACI expression was defective for B cells of all subject

88 nsmembrane activator and CAML interactor:Fc (TACI:Fc).

89 lts demonstrate the critical requirement for TACI in regulating B cell homeostasis.

90 e presently characterized a precise role for TACI in vivo.

91 e data indicate a disparity in the roles for TACI and BAFFR in primary T cell-independent antibody re

92 Thus, our data reveal dual roles for TACI in B-cell terminal differentiation.

93 vitro and intrinsically occurring AAM s from TACI(-/-) macrophages.

94 ated Mcl-1, suggesting that a BAFF/APRIL --> TACI --> COX-2 --> PGE2--> Mcl-1 pathway reduces activat

95 On one hand, TACI modulates ICOS ligand expression and thereby limits

96 s were measured in B cells from heterozygous TACI A144E knock-in mice.

97 gely distinct sets of surface-IgM(+)CD138(hi)TACI(+)CXCR4(+)CD1d(int)Tim1(int) plasma cells expressin

98 How TACI promotes antibody production and inhibits lymphopro

99 How TACI regulates these two opposing conditions is unclear,

100 f the JCI, Romberg and colleagues report how TACI mutations impact B cell activation, removal of auto

101 Unlike the murine gene, human TACI undergoes alternative messenger (m)RNA splicing to

102 The mTACI A144E mutant, like its human TACI A181E counterpart, was expressed on the surface of

103 rt, A181E, disrupt TACI signaling and impair TACI-dependent B-cell functions.

104 These variants impair TACI function, and TACI-deficient mice exhibit a CVID-li

105 on with reduced TACI expression and impaired TACI function, APRIL or BAFF did not activate the classi

106 d reported to be likely mediated by impaired TACI expression affecting B-cell function.

107 More importantly, TACI ligands BAFF or APRIL were unable to induce IgA/IgG

108 The antigen-specific antibodies in TACI-deficient mice were produced in bursts and had high

109 , we examined B cells from mice deficient in TACI, BCMA, and BAFF-R.

110 L1RN, and FIZZ1 were significantly higher in TACI KO Muvarphi than in WT cells.

111 gonist, CpG led to a significant increase in TACI expression and restored TACI-mediated functions.

112 of subjects with CVID who have mutations in TACI but normal immune globulin levels still have detect

113 s down-regulated M2 markers in WT but not in TACI-deficient Muvarphis.

114 st that TACI A181E heterozygosity results in TACI haploinsufficiency with increased susceptibility to

115 ave heterozygous amino acid substitutions in TACI.

116 immunodeficiency-associated gene variants in TACI, BAFFR, ICOS, CD21, LRBA, and CD27 as genetically d

117 oration of the role of genetic variations in TACI in CVID populations has improved our understanding

118 rough MyD88-dependent mechanisms to increase TACI expression, they differ in terms of their downstrea

119 ther Toll-like receptor 9 agonists increased TACI expression and whether an agonistic anti-TACI antib

120 ontrols a B cell-intrinsic, TIR-independent, TACI-dependent pathway for immunoglobulin diversificatio

121 tor by physically interacting and inhibiting TACI and BCMA, members of the tumor necrosis factor (TNF

122 Instead, TACI-deficient QM B cells remained in the cell cycle lon

123 transmembrane activator and CAML interactor (TACI) but not to the BAFF receptor (BAFFR).

124 transmembrane activator and CAML interactor (TACI) influences wild-type TACI function is unclear; dif

125 transmembrane activator and CAML interactor (TACI) mutation C104R, which abolishes ligand binding, fa

126 transmembrane activator and CAML interactor (TACI) result in common variable immune deficiency, a syn

127 Transmembrane activator and CAML interactor (TACI) signals are critical for BAFF-mediated autoimmunit

128 transmembrane activator and CAML interactor (TACI), and CD23 activation markers after TLR9 stimulatio

129 transmembrane activator and CAML interactor (TACI).

130 lating cyclophilin ligand (CAML) interactor (TACI) and B-cell maturation antigen (BCMA), has been sho

131 or and cyclophilin ligand (CAML) interactor (TACI) and B-lymphocyte stimulator (BLyS) provide an earl

132 transmembrane activator and CAML-interactor (TACI), and BAFF receptor-3 (BR3)) for APRIL and the clos

133 modulator and cyclophilin ligand interactor (TACI) and B cell maturation Ag (BCMA), which bind both B

134 modulator and cyclophilin ligand interactor (TACI) and B cell maturation Ag, the early role was attri

135 -modulator and cytophilin ligand interactor (TACI) and B cell maturation antigen (BCMA), on B cells.

136 um-modulating cyclophilin ligand interactor (TACI) are found in 8% to 10% of subjects with common var

137 um-modulating cyclophilin ligand interactor (TACI) controls differentiation of long-lived plasma cell

138 modulator and cyclophilin ligand interactor (TACI) expression.

139 d cyclophilin [corrected] ligand interactor (TACI) is a TNFR family member molecule with a pivotal ro

140 tor and calcium modulator ligand interactor (TACI) is important for T-independent antibody responses.

141 modulator and cyclophilin ligand interactor (TACI) mutations in the pathogenesis of CVID was further

142 modulator and cyclophilin ligand interactor (TACI) often display dysfunctional antibody production.

143 modulator and cyclophilin ligand interactor (TACI) was severely reduced in XID B cells.

144 modulator and cyclophilin ligand interactor (TACI), a member of the TNFR family, required for TI-2 Ab

145 modulator and cyclophilin ligand interactor (TACI), a receptor for BLyS and APRIL, mounted an initial

146 ctivator and cylclophilin ligand interactor (TACI), and also interacts independently with heparan sul

147 modulator and cyclophilin ligand interactor (TACI), B cell maturation Ag (BCMA), and BAFF-R.

148 modulator and cyclophilin ligand interactor (TACI), contribute to common variable immunodeficiency an

149 modulator and cyclophilin ligand interactor (TACI), is a key molecule for plasma cell maintenance and

150 odulating and cyclophilin ligand interactor (TACI)-Ig fusion protein (which neutralizes both BAFF and

151 modulator and cyclophilin ligand interactor (TACI).

152 odulator, and cyclophilin ligand interactor (TACI); B cell maturation Ag (BCMA); and BAFF-R.

153 modulator and cyclophilin ligand-interactor (TACI), which also bind a proliferation-inducing ligand (

154 -cell-conditional mTOR deficiency interrupts TACI signaling via NF-kappaB and cooperation with TLRs,

155 s BLyS and expressed primarily intracellular TACI, and cell surface TACI levels increased following m

156 a requirement for at least one of the known TACI ligands, BAFF and/or APRIL.

157 QM mice that lack TACI produce decreased numbers of IgM (2-fold) and IgG (

158 Moreover, mice lacking TACI were able to clear Citrobacter rodentium, a model p

159 Preterm neonatal B cells expressed less TACI, BCMA, and BAFF-R compared with adult B cells and h

160 nd calcium-modulator and cyclophilin ligand (TACI).

161 lls and pre-B cells transduced with the long TACI isoform retained surface CD19 and immunoglobulin G,

162 These findings demonstrate that low TACI expression may be a critical factor that determines

163 tumor necrosis factor receptor family member TACI (transmembrane activator and calcium-modulator and

164 necrosis factor receptor superfamily member TACI are associated with CVID and autoimmune manifestati

165 PRIL shares two TNF receptor family members, TACI and BCMA, with another TNF homolog, BLyS/BAFF.

166 Here, we report that compared with WT mouse, TACI KO Muvarphis expressed lower levels of Toll-like re

167 rate that C104R and the corresponding murine TACI mutant, C76R, which also does not bind ligand, domi

168 ells cotransfected with wild-type and mutant TACI.

169 nd proteins in vCTB cells but essentially no TACI.

170 immunization of newborn BALB/c mice but not TACI knockout mice with CpG ODN containing (4-hydroxy-3-

171 d that reconstitution with wild-type but not TACI-knockout B cells restored normal CTL responses supp

172 and their receptors BCMA and BAFFR, but not TACI; APRIL/BCMA is enhanced in HCC, compared with norma

173 i phenotype revealed that, in the absence of TACI, Muvarphis adapt the alternatively activated (M2) p

174 The combination of TACI-Ig and CTLA4-Ig resulted in a temporary decrease in

175 is effect, we administered a short course of TACI-Ig with and without six doses of CTLA4-Ig to 18- to

176 Disruption of TACI-mTOR interaction by rapamycin, truncation of the My

177 Fc) that express the extracellular domain of TACI (amino acid [aa] 1-126) restored CTL priming in B-c

178 Here we found that the cytoplasmic domain of TACI encompasses a conserved motif that bound MyD88, an

179 n, truncation of the MyD88-binding domain of TACI, or B-cell-conditional mTOR deficiency interrupts T

180 d in the context of the inhibitory effect of TACI-Ig on B cell maturation at the transitional stage.

181 cells, excess BAFF promotes the expansion of TACI-expressing transitional B cells.

182 the surface and intracellular expression of TACI protein in EBV-transformed B cells of patients and

183 However, another form of TACI exists wherein the N-terminal CRD is removed by alt

184 investigate the effect on B-cell function of TACI A181E heterozygosity in reportedly healthy subjects

185 tudy examined the expression and function of TACI mutations in healthy heterozygous relatives.

186 These studies highlight the importance of TACI signaling for the maintenance of ASCs and protectio

187 t-term IgG secretion occurs independently of TACI as DNA double-strand breaks associated with isotype

188 induce Blimp-1 transiently, independently of TACI.

189 Inhibition of TACI, BCMA, and BAFF-R expression on CLL cells; abrogati

190 /-) mice, expressed half the normal level of TACI on their B cells and exhibited similar defects in a

191 (AdTACI) that produces high serum levels of TACI-Fc fusion protein.

192 es using gene KO mice indicated that loss of TACI affected only T-cell-independent antibody responses

193 To assess how the number of TACI mutations affects B cell activation and tolerance c

194 tory effects correlated with the presence of TACI+ T cells in aggregate and diffuse synovitis and the

195 findings suggest that the high prevalence of TACI deficiency in humans might reflect enhanced host de

196 ucleotides (CpG ODN) led to up-regulation of TACI expression on newly formed, follicular, and margina

197 Thus, the role of TACI mutations in producing the immune defect remains un

198 xpress either the C104R or A181E variants of TACI.

199 ct of its murine equivalent, mTACI A144E, on TACI signaling in transfected cells and on TACI function

200 n TACI signaling in transfected cells and on TACI function in transgenic mice.

201 n of inducible costimulator (ICOS) ligand on TACI-deficient B cells, given that ablation of one copy

202 ansgenic mice expressing the A144E mutant on TACI(-/-) background had low serum IgA levels and signif

203 ine the consequence of the A181E mutation on TACI function, we studied the effect of its murine equiv

204 ich killed targets expressing either BCMA or TACI (P < .01 and P < .05, respectively, cf. control, ef

205 that signaling through BR3, but not BCMA or TACI, activated the alternative nuclear factor of kappa

206 ell generation in mice deficient for BCMA or TACI, respectively, suggested that the interaction of BA

207 treated with a short course of BAFF-R-Ig or TACI-Ig fusion protein.

208 ional B cell defects such as BTK, BAFF-R, or TACI deficiency, were found to have higher BAFF levels t

209 Confirming their M2 phenotype, TACI-KO Mvarphis were unable to control Leishmania major

210 We investigated potential TACI haploinsufficiency by analyzing patients with antib

211 oreover, low doses of a TACI fusion protein (TACI-Fc) that express the extracellular domain of TACI (

212 receptors, BCMA (B cell maturation protein), TACI (transmembrane activator and CAML [calcium-modulato

213 -like antibody responses by linking proximal TACI signaling events with distal immunometabolic transc

214 ffect through cell-surface receptors BAFF-R, TACI, and BCMA.

215 racellular domain of the BAFF-APRIL receptor TACI, was applied in clinical trials.

216 ediated down-regulation of the BLyS receptor TACI (transmembrane activator and calcium modulator and

217 in signaling from the cell surface receptor TACI in lymphocytes, although its role and mechanism of

218 on (CSR) in B cells by engaging the receptor TACI.

219 ited the binding of BLyS to its 3 receptors, TACI, BCMA, and BLyS receptor 3/BAFF-R.

220 BLyS binds to 3 TNF-R receptors, TACI, BCMA, BAFF-R, to regulate B-cell survival, differe

221 BAFF binds three receptors, TACI, BCMA, and BR3, with signaling through BR3 being es

222 ectively, these results suggest that reduced TACI expression is responsible for the unresponsiveness

223 In correlation with reduced TACI expression and impaired TACI function, APRIL or BAF

224 icular and marginal zone B cells up-regulate TACI in response to TLR9 stimulation, only marginal zone

225 to polysaccharide vaccines by up-regulating TACI.

226 CpG prestimulation also restored TACI-mediated signaling in APRIL- or BAFF-stimulated XID

227 ant increase in TACI expression and restored TACI-mediated functions.

228 tive products, but instead reveals selective TACI haploinsufficiency at later stages of B-cell develo

229 oglobulin G, cells transduced with the short TACI isoform completely lost these B-cell characteristic

230 Expression of the short TACI isoform produced intense nuclear factor kappaB acti

231 The short TACI-transduced cells became larger and CD138 positive,

232 However, only subjects with a single TACI mutation displayed a breached immune tolerance and

233 tion of endogenous BAFF and APRIL by soluble TACI and BCMA decoy receptors attenuates the survival of

234 neutralization of BAFF and APRIL by soluble TACI and BCMA decoy receptors could be useful to dampen

235 is study, we show that an endogenous soluble TACI (sTACI) exists in vivo.

236 In the absence of soluble TACI ligands, Ag-activated MZ- and B1-derived blasts lac

237 We report that, although surface TACI expression is usually limited to mature B cells, ex

238 expressed significant levels of cell surface TACI at isolation.

239 imarily intracellular TACI, and cell surface TACI levels increased following monocyte activation.

240 he most highly overexpressed genes were SYK, TACI, CD74, CD82, and CDC42EP5.

241 gnificantly lower in A181E-heterozygous than TACI-sufficient Swedish blood donors never immunized wit

242 cells remained in the cell cycle longer than TACI-proficient QM cells and had impaired plasma cell di

243 We conclude that TACI has dual B cell-autonomous functions, inhibiting pr

244 In this regard, we demonstrate that TACI is inducible early upon B cell activation and this

245 This work demonstrates that TACI preassembles as an oligomeric complex prior to liga

246 Here, we determined that TACI-deficient mice have low baseline levels of Ig in th

247 eir receptors in newborn mice and found that TACI expression on B lymphocytes was dramatically reduce

248 In addition, we found that TACI expression requires activation of the ERK1/2 pathwa

249 We found that TACI interacts with the cleaved, mature forms of TLR7 an

250 Although we have found that TACI is dispensable for controlling B. hermsii infection

251 Surprisingly, we found that TACI(-/-) mice are not impaired either in specific antib

252 Our studies indicate that TACI acts at a remote time from activation because TACI

253 ype 3 serotype pneumococcus, indicating that TACI is required for T cell-independent antibody respons

254 thus resolving the longstanding paradox that TACI may have both B cell-inhibitory and -stimulatory fu

255 Furthermore, we show that TACI is expressed by MB cells and PCs, as well as a subp

256 Together, we show that TACI is sequentially processed by a disintegrin and meta

257 We show that TACI promotes sustained Blimp-1 expression by B cells re

258 Our results showing that TACI induces and maintains Blimp-1 provide, for the firs

259 e antigen, it has previously been shown that TACI is critical for T cell-independent antibody respons

260 These results suggest that TACI A181E heterozygosity results in TACI haploinsuffici

261 These results suggest that TACI mutations can result in CVID and IgAD.

262 ted B cells, APRIL does not, suggesting that TACI but not BLyS receptor 3 may share survival promotin

263 formation in Taci(-/-) mice, suggesting that TACI is more important for the survival of plasma cells

264 es do not present with CVID, suggesting that TACI mutations influence CVID pathogenesis via dominant

265 by an activated, cycling phenotype, and the TACI(+) cell subset is specifically enriched for autorea

266 vation of a chimeric receptor containing the TACI intracellular domain induces apoptosis.

267 in 200 blood donors are heterozygous for the TACI A181E mutation.

268 d not produce IgG and IgA in response to the TACI ligand APRIL, probably reflecting impaired isotype

269 ion signals by stimulating CLL cells through TACI, BAFF-R, and BCMA receptors.

270 ing a need for B-cell-DC cooperation through TACI-BLyS during CTL first encounter with antigens in vi

271 ockout models suggest that signaling through TACI is critical to B-cell homeostasis.

272 Thus, TACI mutations may favor CVID by altering B cell activat

273 APRIL with the TNF family receptors (TNFRs) TACI, BCMA, and BAFF-R are crucial to TI antibody respon

274 BR3, while the later role was attributed to TACI/B cell maturation Ag.

275 ting of one APRIL and two BAFF (ABB) bind to TACI and BCMA and weakly to BAFFR in accordance with the

276 Even a brief exposure to TACI-Ig had a beneficial effect on murine SLE; CTLA4-Ig

277 Transfer of WT Muvarphis to TACI KO mice was sufficient to significantly reduce dise

278 binding, fail to produce Igs in response to TACI ligand.

279 rate and secrete IgG1 and IgA in response to TACI ligation.

280 Triggering TACI by an agonistic antibody showed loss of activation-

281 cific variant of APRIL, APRIL-R206E, and two TACI-selective variants, D132F and D132Y.

282 iduals and CVID patients carrying one or two TACI mutations.

283 nsiveness in patients with one, but not two, TACI mutations enables autoimmune complications.

284 CAML interactor (TACI) influences wild-type TACI function is unclear; different models suggest eithe

285 the B cell developmental subsets undergoing TACI-dependent activation in settings of excess BAFF rem

286 ation by delivering nonredundant signals via TACI and BCMA receptors through both autocrine and parac

287 clearance of Leishmania from cells only when TACI is expressed.

288 rtcomings of host response in newborns where TACI expression is reduced and in combined variable immu

289 ned variable immunodeficiency patients where TACI signaling is ablated.

290 that together reveal the mechanism by which TACI engages high affinity ligand binding through a sing

291 inant BAFF and anti-IgM in an assay in which TACI-Fc fusion protein inhibits B-cell proliferation.

292 tward signs of CVID, and it is not clear why TACI deficiency in this group does not cause disease.

293 Treatment of B cells with TACI agonistic antibodies inhibits proliferation in vitr

294 G (1.6-fold) NP-specific ASCs, compared with TACI-positive QM mice in response to immunization with N

295 roenvironment and that, upon engagement with TACI, APRIL mediates activation of the phosphatidylinosi

296 B cells from individuals with TACI mutations expressed TACI but did not produce IgG an

297 s not bind ligand, dominantly interfere with TACI signaling.

298 In GC+ synovitis, treatment with TACI:Fc resulted in GC destruction and marked inhibition

299 did not interfere with ligand binding by WT TACI, suggesting that they may act by disrupting ligand-

300 ent on preassociation of the mutants with WT TACI in the absence of ligand.